Compounds of structural formula I are known from U.S. Pat. Nos. 4,677,115 and 4,797,413 and known to be topically effective carbonic anhydrase inhibitors useful in the treatment of ocular hypertension. However, the processes described for their preparation result in diastereomeric or racemic products which must be separated and resolved, with concommitant loss of at least 50% of the product, to obtain the most active enantiomer.
The catalyst used in the novel process of this invention is an oxazaborolidine catalyst. Catalysts of this type have been described by Corey et al., J. Amer. Chem. Soc. 1987, 109, 7925-7926; J. Amer. Chem. Soc. 1987, 109, 5551-5553; J. Org. Chem., 1988, 53, 2861-2863; Tetrahedron Lett., 1989, 30, 5547-5550; Tetrahedron Lett., 1989, 30, 6275-6278; Tetrahedron Lett., 1990, 31, 611-614; Youn et al., Tetrahedron Lett., 1988, 29, 4453-4456; Itsuno, J. Chem. Soc., Perkin Trans. 1, 1984, 2887; J. Chem. Soc., Chem. Comm., 1983, 469; and J. Org. Chem., 1984, 49, 555.
Now with the present invention there is provided an enantioselective synthesis which obviates the production of the less active enantiomer and the concommitant loss of material that results from the discarding of that less active enantiomer and the usual material losses encountered in separation of optical isomers and isolation procedures.